In 1968, glycosylhemoglobin (HbAlc) which is one of the minor components of hemoglobin was identified in vivo and was found to increase in patients diagnosed with diabetes. This discovery has aroused interest in the biological meaning of the Maillard reaction and, particularly, in the relationship between aging and diabetes.
The Maillard reaction may be classified into a former stage and latter stage. In the former stage a Schiff base is formed by the condensation reaction between an amino group of a protein and an aldehyde group of a reducing sugar. The Schiff base is stabilized as a result of an Amadori rearrangement. In the latter stage, the former stage product undergoes a long series of reactions, to obtain the latter-stage products of the Maillard reaction. The latter stage products are characterized by fluorescence, a color change to brown, and molecular crosslinking. The fluorescence, which is known as one of the characteristic changes found in the latter-stage products of the Maillard reaction, is significantly higher in diabetic patients than in healthy or non-diabetic persons. The fluorescence is suggested to have a correlation with the onset of diabetic complications such as diabetic nephrosis, arteriosclerosis, nervous disturbance, retinal diseases, cataracts, etc.
However, basic structures for the latter-stage products of the Maillard reaction have not been clarified yet. Accordingly, there have been many ambiguous points with respect to mechanisms for the nonenzymatic saccharization and crosslinking of proteins caused by aging and diabetes.
The present inventors have conducted continued studies on the mechanisms of nonenzymatic saccharization and crosslinking of proteins and, as a result thereof, found novel pyridinium derivatives which relate to the basic structure of the latter-stage products of the Maillard reaction. The pyridinium derivatives of the present invention are useful in the diagnosis of diabetes, diabetic complications, aging, and diseases associated with aging. The pyridinium derivatives are also useful for the evaluation of the effectiveness of pharmaceuticals for treatment of diabetes, diabetes related diseases, aging and its accompanying diseases.